Be aware that the vast majority of individuals screened had no evidence of mental stress-induced ischemia and were thus ineligible for this study.

Six weeks of treatment with the antidepressant escitalopram (Lexapro) resulted in a lower rate of mental stress-induced chest pain in patients with stable coronary heart disease, a small randomized study found.

By the study's end, more patients taking escitalopram had no mental stress-induced myocardial ischemia during three mental stress activities compared with patients taking placebo (34.2% versus 17.5%), according to Wei Jiang, MD, of Duke University Medical Center, and colleagues.

In addition, those taking escitalopram, a selective serotonin reuptake inhibitor (SSRI), had a 2.6 times higher rate of no mental stress-induced chest pain compared with the placebo group (P=0.04), the researchers wrote in the study published in the May 22/29 issue of JAMA.

The absence of mental stress-induced chest pain was accompanied by both a reduction in mental stress-induced wall motion abnormality and a decrease in left ventricular ejection fraction (LVEF) of 8% or more.

The antidepressant also led to lower hemodynamic responses to mental stress between the two groups, with significant differences in systolic blood pressure (P=0.03) and heart rate (P=0.005).

When patients in the escitalopram group were subject to mental stress after the 6-week intervention, results showed they had greater improvements in certain measures of psychological functioning, including for positive affect (P=0.05).

Taking escitalopram also was associated with several positive changes in cardiovascular markers, including reducing the number of platelet serotonin receptor transporters.

Mental stress-induced myocardial ischemia is typically diagnosed by certain changes in the heart: new wall motion abnormality, reduced LVEF, ischemic changes on ECG tests, or a combination of these symptoms.

However, little is known about how to treat it, with inconclusive and conflicting results in previous studies looking at interventions.

Jiang and colleagues therefore led the Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study, a randomized, double blind, placebo controlled clinical trial. They enrolled participants with existing stable coronary heart disease from July 2007 through August 2011 at a large tertiary medical center.

The researchers used three mental stressor tasks -- a tricky mental math task; tracing a diagram of a star while looking at hand movement as a reflection in a mirror; and telling a story about a situation that evoked anger or sadness -- to determine the occurrence of stress-induced ischemia before and after the study period. Participants also underwent a stress treadmill test, as well as other hemodynamic monitoring.

The 112 eligible patients were randomized 1:1 to receive escitalopram or placebo over 6 weeks. Eight patients had dropped out of the intervention group and seven from the control group.

The mean age was 64, more than three-quarters were white, and only 20% were women.

Most of the patients were taking aspirin, with close to half taking another antiplatelet agent. The majority were taking angiotensin-converter enzyme inhibitors and beta-blockers, with 20% or less taking angiotensin receptor blockers or calcium channel blockers. Better than 95% were taking statins, and 93% had documented hyperlipidemia.

Current thinking pegs one of the underlying pathological processes of mental stress-induced myocardial ischemia as constriction of micro-coronary arteries -- a kind of endothelial dysfunction "resulting from dysregulation of the central nervous system and hypothalamic-pituitary-adrenal axis system in response to emotional stress."

However, Jiang and colleagues noted that escitalopram reduced mental stress-induced myocardial ischemia that could not be modified by conventional ischemic agents.

This suggests that "enhancing central synaptic availability of serotonin may be an important step in management of coronary heart disease," researchers concluded.

"We've known for years that stress can cause cardiac death," said senior author Christopher O'Connor, MD, director of the Duke Heart Center and chief of the Division of Cardiology, in a JAMA video interview. He said that a study he was involved in found a "significant uptick in heart attacks" associated with a drastic downturn on Wall Street.

O'Connor also noted the effect the antidepressant had on the platelet function, which is "perhaps one way the ischemia could be reduced."

Study limitations included the relatively small sample size and short follow-up, a lower-than-expected study power, a considerable number of dropouts, not evaluating individual mental task potency, and a lack of generalizability for the results to pertain to different patient populations.